Post-operative infections of implants, such as total joint implants following surgery is frequent, occurring in 1-2% of all cases. The present diagnosis of infected surgical and medical implants is not always successful. The clinical presentation is often problematic. Presently, diagnosis depends on both clinical judgment and reliance on standard serologic clinical tests. These tests include sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBC), analysis of aspirated joint fluid, and interpretation of intraoperative tissue and fluid test results. Even having evidence of implant loosening stemming from x-ray identification and pre-operative needle aspirations can be negative for microbes and cultures of adjacent tissue at the time of surgery may be negative for any bacteria. Diagnosis, therefore, can be complicated and based on a combination of findings, rather than a single one. Even with these available diagnostic tests, an infected implant often escapes detection. Clinically, the presentation may not be evident and currently, there is no single or combination of tests accurate enough to diagnose an infected implant.
The many various methods may fail to identify the source of the infection in spite of clinical evaluation, laboratory testing, radiological scans and even molecular biology. One of the main reasons for difficulty in diagnosis is due to biofilm formation. Common biofilms stem from pathogenic bacteria and yeast. The biofilm forms a firm attachment to the implant that resists mobilization. Recently, it has been reported that the only way to mobilize these biofilms is after surgical removal of the prosthesis and subjection of the removed implant to ultrasound (see Trampuz et al., NEJM. 357, pp. 654-663, 2007).
Once an implant is diagnosed as being infected, there are few good treatment options. Traditional treatments include antibiotic therapy, irrigation, debridement, arthrodesis and even amputation in life threatening situations. Commonly, the treatment of an infected implant is surgical removal, placement of a temporary antibiotic impregnated spacer, followed by one or more surgeries to replace another implant with the attendant risks and morbidity. Thus, patients having an infection often require complex and expensive treatment that often has low outcome. Each of these methods are either unsuccessful or are met with complications. The humanitarian and societal costs are high for the diagnosis and treatment of loose and or infected total joints. These costs start with the initial diagnostic dilemmas that delay definitive treatment or result in erroneous therapies. There is, therefore, an unmet need for more effective methods of diagnosing an infected implant that is in a patient and treating the infected implant. Described herein are effective methods for detecting an infection of an implant and compounds and compositions for treating the infected implant that solves this unmet need.